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Co-evolved genes improve the biosynthesis of secondary metabolites

A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.

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Fig. 1: PQQ cluster-enhanced natural product production.


  1. Gavriilidou, A. et al. Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes. Nat. Microbiol. 7, 726–735 (2022). This paper reports secondary metabolite biosynthetic diversity in bacteria.

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  2. Challis, G. L. & Hopwood, D. A. Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc. Natl Acad. Sci. USA 100 (Suppl. 2), 14555–14561 (2003). This review discusses the idea that synergy drives evolution of multiple secondary metabolite BGCs contributing to host competitiveness.

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This is a summary of: Wang, X. et al. Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis. Nat. Metab. (2024).

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Co-evolved genes improve the biosynthesis of secondary metabolites. Nat Metab 6, 789–790 (2024).

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